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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid eye movement (REM) sleep behavior disorder (RBD), which is characterized by dream-enacted, sometimes violent and aggressive, behaviors was firstly reported by Schenck and his colleagues in 1986; thereafter, it was incorporated as parasomnia in the International Classification of Sleep Disorders 1st edition (ICSD-1). The polysomnographical hallmarks of RBD include intermittent/sustained loss of the skeletal muscle atonia of REM sleep (REM sleep without atonia [RWA]); further, this finding has been mandatory in the diagnostic criterion (requiring polysomnographic [PSG] monitoring) in the ICSD-2 in 2005. The animal equivalent of RBD was previously described by Jouvet's and Morrison's groups, dated back to 1965, when Jouvet's group firstly created experimentally lesioned cats (in the bilateral pontine tegmentum areas) presenting with "oneiric behaviors". In 1970s Hishikawa's group had also described peculiar sleep state in alcoholics and other subjects of drug withdrawal with rapid eye movements and tonically increased chin muscle activity (reffered to as "Stage 1-REM with tonic EMG" [Stage 1-REM]). It was difficult to determine from the polysomnographical features whether Stage 1-REM was REM sleep or not, as this state did not preserve proper cyclic appearance of REM sleep. They also reported Stage 1-REM in patients with Shy-Drager syndrome in 1981. The latter finding of Hishikawa's group, together with RBD observed in multiple system atrophy (MSA) reported by other groups, could be best explained by the experimental cat model because of its presumed extensive brainstem pathology. However, neurophysiology of withdrawal states has not been well understood; therefore, Stage 1-REM should be reappraised from new perspectives. After 1990, more extensive studies on RBD revealed that about half of RBD cases were associated with neurological disorders, especially neurodegenerative diseases pathologically known as syncleiopathies (Parkinson disease [PD], dementia with Lewy bodies, and MSA). In addition, it has been shown that a substantial number of idiopathic RBD (iRBD) patients eventually developed Parkinsonian diseases. In accordance with accumulative data indicating that various non-parkinsonian features can precede the onset of motor symptoms of PD (or pathologically Lewy body diseases), a search of early PD markers in patients with iRBD has been performed. The results of the studies support the hypothesis of RBD as an early sign of a neurodegenerative disorder. More recently, it was reported that RBD is frequently symptomatic of narcolepsy, although the pathophysiological mechanism of this state was still unknown. RBD in stroke patients have been anecdotal; however, under such conditions, specific lesion studies can be possible, as data in the experimental RBD rats have been accumulated during these few years. In conclusion, RBD is observed in a wide range of neurological disorders, and the causative mechanism of RWA and behavioral manifestations may not only be attributable to brainstem lesions. RBD is not a homogeneous clinical entity, and further refinement of its diagnostic classification is warranted to avoid diagnostic confusion.
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PMID:[Historical overview of REM sleep behavior disorder in relation to its pathophysiology]. 1951 16

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.
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PMID:Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations. 1967 85

Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood. Extensive loss of the hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and partial loss of these cells may contribute to the sleepiness of Parkinson disease and other disorders. We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI. This observation highlights the often overlooked hypothalamic injury in TBI and provides new insights into the causes of chronic sleepiness in patients with TBI.
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PMID:Loss of hypocretin (orexin) neurons with traumatic brain injury. 1984 5

Circa 1660 several favorable factors, instrumental to the invention of neurology, converged at the University of Oxford. Animals and men were believed to have a material soul whose functions throughout the nervous system were accessible to research. In 1659 inductive methods were introduced in clinical medicine by Thomas Willis, the founder of English epidemiology and biochemistry. The Vertuosi,who later founded the Royal Society, performed chemical experiments in teams, and Willis, head of their laboratory, gained experience in teamwork. In 1658 J.J. Wepfer published his method of dye injection in cerebral vessels at autopsy, and Christopher Wren had already experimented with intravenous injections. William Petty had performed dissections at Leiden, training with Francis Sylvius's brain and comparative anatomy. Petty came to Oxford in 1650, began to study chemistry with Willis, and instructed him in Sylvius's methods of cerebral and comparative anatomy. Willis continued this work with a team of highly qualified colleagues, Wren included, and published the first monograph on brain anatomy, Cerebri anatome, in 1664. This Latin book, illustrated by Wren, came out in four editions in the first year, and was reprinted up to 1720. It contained a definition of reflex action, the recognition of the general functions of cortex, white matter, and brain tracts, a complete description of the autonomic nervous system, Willis's new term "Neurologia," and his promise to follow up with his "Psychologia." He presented the latter in 1672 as De anima brutorum, a book on the material soul of animals and man as the carrier of all functions of the nervous system. There was a physiological part, a textbook of neurophysiology, and a pathological part, a compendium of neurological and psychiatric syndromes, with early descriptions of myasthenia, restless legs, narcolepsy, dissociative and bipolar disease, and general paralysis of the insane. In 1667 he published a book on convulsive diseases, in which he described the blood-brain barrier, epileptic and hysterical brain disorders, and Parkinson's disease. Thus Willis recognized and presented the key themes of the future specialty.
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PMID:Chapter 8: the development of neurology and the neurological sciences in the 17th century. 1989 11

Narcolepsy is a neurologic sleep disorder characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement (REM) sleep such as cataplexy, sleep paralysis and hypnagogic hallucinations. Although epidemiologic studies show that it is nearly as widespread as Parkinson's disease or multiple sclerosis, narcolepsy is often not much known and confused with other neurologic disorders and psychiatric pathologies. The hard psychosocial impact on patient's life can be mitigated by an early diagnosis and by a targeted pharmacological treatment alleviating the most debilitating symptoms. Through a deep assessment of international literature we traced an updated picture of narcoleptic disorder in order to provide a useful tool of neurobiological, clinical, and therapeutic knowledge. Particular attention has been turned to the new discoveries on the possible role of the neuropeptide orexin in the genesis of narcolepsy, which open new pharmacological and research frontiers in this field.
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PMID:[Narcolepsy]. 2006 34

Altered sleep is a common non motor symptom in Parkinson's disease. Sleep dysfunction has been reported to occur in 60-90% of all PD patients, having a detrimental impact on quality of life and increasing disability. alpha-Synuclein deposits in the lower brainstem affecting autonomic and sleep regions have been identified in the pathophysiology. The resultant non motor symptoms such as REM sleep behaviour disorder (RBD) can precede the motor symptoms by years. RBD is violent, enacted dreams that expose the patient or their sleeping partner to night-time injuries. Excessive daytime sleepiness, sometimes with a narcolepsy-like phenotype, is a common occurrence in PD, owing to lesions in the arousal systems of the brain. Restless legs syndrome and sleep disordered breathing can all affect daytime alertness of PD patients. Autonomic deregulation can also negatively affect sleep patterns, by adding to night-time wakening and disrupting sleep.
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PMID:Sleep dysfunction and role of dysautonomia in Parkinson's disease. 2008 18

Non-motor symptoms in Parkinson's disease (PD), such as excessive daytime sleepiness, 'sleep attacks', insomnia, restless legs syndrome and rapid eye movement sleep behavior disorder, are common and provide a challenge to treatment. These sleep symptoms are also described in patients suffering from the sleep/wake disorder, narcolepsy. The International Classification of Sleep Disorders (ICSD-2) narcolepsy criteria uses a number of markers for diagnosis, of which lack or deficiency of cerebrospinal fluid (CSF) hypocretin-1 levels is a key marker. Hypocretin neurons prominently located in the lateral hypothalamus and perifornical nucleus have been proposed to interact with mechanisms involving sleep and arousal. Low hypocretin-1 levels in the CSF have been shown to correlate with hypothalamic hypocretin cell loss in narcolepsy and other forms of hypersomnia; therefore, it has been proposed that degenerative damage to hypocretin neurons (such as in PD) may be detected by low CSF hypocretin-1 concentrations, and may also explain the sleep symptoms experienced by some PD patients. To date, there is mixed conflicting data describing hypocretin-1 levels in the CSF of patients with parkinsonism associated with sleep symptoms, with most studies showing no significant decrease when compared with controls. However, hypocretin-1 CSF deficiency has been shown in some studies to be more prominent in PD patients with sleep symptoms versus those without. Notably, the hypocretin system has been shown not to be selectively disrupted, with one study showing melanin concentrating hormone cell loss in the same patients with hypocretin loss. It is likely that hypocretin deficiency in PD patients occurs secondary to collateral damage caused by the neurodegenerative process involving the hypothalamus. Awareness of narcoleptic events in PD is important for driving related advice, in addition to the possible use of dopamine D3 receptor active agonists.
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PMID:Narcolepsy in Parkinson's disease. 2051 4

Sleep disorders are observed in Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease; however, the underlying mechanisms are unclear. Reduced hypocretin (orexin) levels are reported in Parkinson's disease and sleep disorders, including narcolepsy; however, its levels in dementia with Lewy bodies and Alzheimer's disease and its relationship with sleep disturbances in these disorders remain undetermined. We examined hypocretin levels in dementia with Lewy bodies and Alzheimer's disease cases and correlated these with sleep habits and clinical characteristics. Although limited hypocretin alterations were observed in Alzheimer's disease, we show reduced neocortical hypocretin immunoreactivity in dementia with Lewy bodies patients correlating with hypersomnolence and alpha-synuclein levels. These results suggest the involvement of hypocretin in sleep disorders in dementia with Lewy bodies.
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PMID:Reduced hypocretin (orexin) levels in dementia with Lewy bodies. 2053 Dec 37

Non-ergot-type dopamine receptor agonists such as ropinirole are used for the treatment of Parkinson disease, but they occasionally show serious side effects including sleep attacks and daytime sleepiness. These symptoms are reminiscent of narcolepsy, a major sleep disorder. Because narcolepsy is thought to result from deficiency of a hypothalamic neuropeptide orexin, we examined whether ropinirole affected the integrity of orexin-containing neurons, using organotypic slice culture of rat hypothalamus. Application of ropinirole induced a significant decrease in the number of orexin-immunoreactive neurons. The same treatment showed no significant effect on the number of melanin-concentrating hormone-immunoreactive neurons. The decrease of orexin-immunoreactive neurons was reversible after washout of ropinirole and was not accompanied by induction of cell death. Antagonism of dopamine D(2) receptors and of serotonin 5-HT(1A) receptors attenuated the effect of ropinirole, suggesting involvement of these receptors in depletion of orexin. On the other hand, a moderate concentration of N-methyl-d-aspartate that excited orexin neurons counteracted the effect of ropinirole on the number of orexin-immunoreactive neurons. These results suggest that ropinirole can cause deficiency of orexin by inhibiting excitatory activities of orexin neurons, which may be relevant to the adverse actions of this drug on sleep and wakefulness.
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PMID:An anti-Parkinson drug ropinirole depletes orexin from rat hypothalamic slice culture. 2072 17

The histaminergic system fulfills a major role in the maintenance of waking. Histaminergic neurons are located exclusively in the posterior hypothalamus from where they project to most areas of the central nervous system. The histamine H(3) receptors are autoreceptors damping histamine synthesis, the firing frequency of histamine neurons, and the release of histamine from axonal varicosities. It is noteworthy that this action also extends to heteroreceptors on the axons of most other neurotransmitter systems, allowing a powerful control over multiple homeostatic functions. The particular properties and locations of histamine H(3) receptors provide quite favorable attributes to make this a most promising target for pharmacological interventions of sleep and waking disorders associated with narcolepsy, Parkinson's disease, and other neuropsychiatric indications.
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PMID:Histamine H3 receptors and sleep-wake regulation. 2086 2


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